Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

Background

Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone.

Objectives

The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates.

Patients and Methods

81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations.

Results

12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients.

Conclusions

HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.     

Occult Hepatitis C Virus Infection in Patients With Autoimmune Hepatitis

Background:

Occult hepatitis C virus infection (OCI) is recognized by finding hepatitis C virus (HCV) RNA in hepatocytes without detectable anti-HCV antibodies and viral RNA in plasma. Autoimmune hepatitis (AIH) is a chronic and generally progressive disease without exactly-identified etiology.

Objectives:

This study aimed to determine the prevalence of OCI among patients with AIH and to evaluate the tests used to rule out HCV infection in diagnosing AIH.

Patients and Methods:

Between July 2012 to February 2013, 35 Iranian patients with AIH who attended Tehran Hepatitis Center were investigated. For identifying OCI, detection of HCV RNA in both ultracentrifuged serum samples and peripheral blood mononuclear cells (PBMCs) was used. Data analysis was performed using SPSS.

Results:

Six males and 29 females with mean disease duration of 77.1 ± 39.5 month and mean age of 43.62 ± 12.67 years were investigated. All cases were negative for anti-HCV antibody and we could not find any HCV RNA in ultracentrifuged serum samples and PBMCs.

Conclusions:

With our laboratory diagnostic method, it seems that there are no cases of OCI in patients with AIH. However, we recommend further studies with more samples and more precise laboratory method.     

Occult Hepatitis B Virus Infection in Patients With Chronic Hepatitis C Treated With Antiviral Therapy

Background

Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver and/or in the serum of patients with negative results of hepatitis B s antigen (HBsAg) test with or without serological markers of previous viral exposure. The impact of OBI in patients with chronic hepatitis C (CHC) is still unclear.

Objectives

The Aim of this study was to assess OBI prevalence and its potential implications on treatment outcome in a cohort of patients with CHC underwent standard antiviral therapy.

Patients and Methods

Baseline serum samples from 137 HBsAg-negative CHC patients treated with pegylated-interferon and ribavirin (73 Responders/74 Non Responders),were retrospectively analyzed for HBV status.

Results

Seventy-three patients (53.3%) showed markers of previous exposure to HBV. HBV DNA was detected in 2 of 137 serum samples (1.5%), both carrying HBV antibodies. Liver biopsies and post-therapy sera were available for 35 patients (12 Responders/23 Non Responders). HBV DNA sequences were found in 13 of 35 specimens (37.1%), all of patients with HBV DNA negativity in basal and post-therapy serum samples. Among OBI-positive patients, 5 (38.5%) carried serological markers of HBV infection. Regarding therapy outcome, in the OBI-positive group there were 5 of 13 (38.5%) sustained virological responders (SVR) compared to 7 of 22 (31.8%) in the OBI-negative one.

Conclusions

Despite the high prevalence rate of liver HBV DNA in patients with CHC, SVR was not affected by occult HBV infection.     

Seroprevalence of Hepatitis Viruses B, C, D and HIV Infection Among Hemodialysis Patients in Kerman Province, South-East Iran

Background

The prevalence of hepatitis viruses in hemodialysis patients has been reported to be much greater than in the general population. Attention to local data, effectively guides health planners so that they can control infections and prevent nosocomial transmissions.

Objectives

This cross sectional study was carried out to determine the prevalence of hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) viruses, as well as the human immunodeficiency virus (HIV) in dialysis centers in the Kerman Province, in the southeast of Iran.

Patients and Methods

All hemodialysis patients (n = 228) in 7 centers were enrolled in the study. Hepatitis B surface antigens (HBsAg), HCV antibodies (Ab), HDV Ab and HIV Ab were measured using specific enzyme linked immunoassay kits (ULTRA kit, bioMérieux, France) and confirmed by a qualitative PCR assay.

Results

The studied group was comprised of 92 (40.4%) females and 136 (59.6%) males. The mean age of the patients was 51 ± 9.5 years and the duration of hemodialysis was 39.7 ± 7.9 months. Positive HBsAg was found in 7% of cases, HCV Ab in 7%, and patients with both viruses were detected in 1.7% cases. HIV Ab and HDV Ab were negative in all cases. Out of the other risk factors, frequency of blood transfusions was significantly correlated with positive HCV Ab (P < 0.008).

Conclusions

Prevalence of HBV and HCV in hemodialysis patients was moderate to low in the Kerman Province, as in other parts of the country. Strict adherence to protective measures could lead to even lower rates.     

丙型肝炎病毒感染人单核细胞系U937的研究

利用HCV RNA阳性血清感染人类单核细胞（U937），并利用RT－PCR测定感染后的产物，于感染后的第2天、第4天和第7天发现HCV RNA的正、负链。结果表明，采用本方法可以建立HCV RNA体外感染人类单核细胞的模型，并有病毒复制现象。     

Prevalence of Occult Hepatitis B Virus in Plasma and Peripheral Blood Mononuclear Cell Compartments of Patients With Chronic Hepatitis C Infection in Tehran-Iran

Background

Occult hepatitis B virus (HBV) infection (OBI) is frequently reported in patients with chronic hepatitis C virus (HCV) infection. An association between OBI and more liver damage, cirrhosis, hepatocellular carcinoma, and reduced response to interferon therapy in patients with HCV infection is suggested.

Objectives

The aim of this study was to determine the prevalence of occult HBV, and evaluate its clinical influence on patients with chronic HCV.

Patients and Methods

A cohort study including50 patients with positive results for HCV, and negative results for HBsAg tests was performed. The patients were divided into two groups: one group had positive results for both HCV and occult HBV tests (n = 18), and the other had positive results for HCV, but negative findings for occult HBV (n = 32). All were treated with PEG-IFN alpha-2a and Ribavirin. Presence of HCV RNA was followed in these patients.

Results

HBV-DNA was detected using nested-PCR in 20% of plasma and 32.6% of peripheral blood mononuclear cell (PBMC) compartments. No significant differences were observed between patients with and without occult HBV for sex, age, duration of HCV infection, histological markers, presence of anti-HBc, HCV viral load, and HCV genotype. The response rate was significantly higher in patients with positive results for HBV-DNA test compared to those with negative findings (100% vs. 71.9 %, P < 0.05).

Conclusions

In conclusion, occult HBV was found in 36% of patients with negative results for HBsAg, but positive results for HCV. Detection of HBV-DNA in both PBMCs and plasma together in comparison with plasma alone provided more true identification of OBI.The SVR rate was significantly higher in coinfected patients than mono-infected ones.     

Prevalence and Risk Factors of HIV,Syphilis, Hepatitis B and C Among Female Prisoners in Isfahan,Iran

Background

Female prisoners are at risk of acquiring sexually transmitted infections (STIs). There has been no previous study regarding the epidemiological status of STIs among female prisoners in Isfahan, central Iran.

Objectives

The aim of this study was to investigate the prevalence and risk factors of the aforementioned infections among women incarcerated in the central prison, Isfahan, to determine appropriate prevention measures.

Patients and Methods

In a cross-sectional study, all of the 163 women incarcerated in the central prison, Isfahan in 2009, were voluntarily enrolled by the census method. After completing a checklist consisting of demographic, social, and risk factors, a 5ml blood sample was taken from each individual. The sera were analyzed for markers of the hepatitis B virus (HBV; HBsAg, HBsAb, HBcAb), hepatitis C virus (HCV; HCV antibodies), human immunodeficiency virus (HIV; HIV antibodies), and syphilis (RPR). Confirmatory tests were performed on HCV antibody-positive cases.

Results

The mean age of the participants in the study was 34.54 ± 11.2 years old, 94.3% of these women were Iranian, and many of them had only a primary level of education. The prevalence of HBsAg, HBcAb, HBsAb, and HCV antibodies were; 1.2%, 7.4%, 12.9% and 7.4% respectively. No positive RPR or HIV antibodies were detected.

Conclusions

A significant relationship was seen between the HCV antibody, drug injection and illegal sex in the women, and also between HBc-Ab and drug injection. Regular screening, educational programs, and facilitation of access to suitable treatment care should be widely implemented in the prison population. Testing for immunity against HBV should be considered on admission, and afterwards vaccination of all prisoners and an appropriate preventative approach should be applied.     

Prevalence and Risk Factors of HCV/HIV Co-Infection and HCV Genotype Distribution in North-Eastern Poland

Background:

HIV/HCV co-infection predisposes to accelerated liver damage and increased both liver-related and unrelated morbidity and mortality in patients with HIV infection.

Objectives:

The aim of this study was to evaluate the prevalence of HCV infection, seropositivity, risk factors and genotype distribution among treated HIV positive patients. Furthermore, the occurrence and causes of deaths were analyzed.

Patients and Methods:

Adult HIV-1 infected patients, with at least one antiHCV result, treated in one of Polish HIV/AIDS reference centers, participated in this cross-sectional study.

Results:

Four hundred and fifty seven patients with a median age of 38 years (ranged 23 - 72), and predominantly male (76.6%) were enrolled in the study. Anti-HCV antibodies were detected in 325 individuals (71.1%). HCV RNA was detected in 207 of the 233 patients tested (88%). The HCV genotype analysis (n = 193) demonstrated almost equal distribution with slight genotype 1 domination as 37.3%, mainly 1b, followed by genotypes 3 as 32.1% and 4 as 30.6%. No association was found between HCV genotype and route of HIV acquisition. In univariate analysis, higher HCV seropositivity was related to male sex, intravenous drug use (IDU), mode of HIV transmission, history of drug and alcohol abuse and imprisonment. In multivariate analysis, only being injection drug user (P = 0.0001), imprisonment (P = 0.310) and younger age at the HIV diagnosis per each year (P = 0.025) were identified as risk factors for HCV infection. Sixty three deaths were reported; no association was found between HCV seropositivity and death prevalence.

Conclusions:

HIV/HCV co-infection is an important medical problem in North-Eastern Poland. A history of incarceration and younger age at HIV diagnosis were additional to IDU risk factors for HCV seropositivity in this cohort.     

Distribution of Hepatitis C Virus Genotypes in Bahrain

Background:

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide, making it one of the world’s major infectious diseases. There are no published population based studies about the prevalence of HCV genotypes in Bahrain.

Objectives:

Therefore, the aim of the present study was to investigate the prevalence and distribution of HCV genotypes and subtypes among a large sample of patients with chronic HCV infection in Bahrain.

Patients and Methods:

Serum samples were collected from 202 HCV positive patients; of them 128 had a viral load (> 500 IU/mL) suitable for the type-specific genotyping assay. Gender-wise and age-wise differences in the distribution of HCV genotypes were determined by Chi Square and Fisher’s Exact tests.

Results:

The predominant genotype among Bahraini patients was type 1 (36.71%), followed by genotypes 3 and 4 (15.6% each) and the lowest frequency was found for genotype 2 (3.9%). Among genotype 1, subtype 1b had the highest frequency (21.09%), followed by subtype 1a (14.06%). Among genotype 3, subtype 3a had the highest frequency (11.72%), while among genotype 4, most of subtypes were undetermined. The frequency of all different HCV genotypes was higher in male patients compared to female patients. Genotype 1 was most common in the age group of 51 - 60 years (38.3%), genotype 2 in 21 - 30 years (60%) and genotype 3 in 51 - 60 years (30%), while genotype 4 was most frequent among the age group > 61 (40%).

Conclusions:

The most common HCV genotype in Bahrain was subtype 1b followed by 1a and 3a. Further studies involving sources of transmission in Bahrain are required to enhance control measures for HCV infection.     

Phylogenetic Analysis of Torque Teno Virus in Hepatitis C Virus Infected Patients in Shiraz

Background

Torque teno virus (TTV) was the first human Circoviridae detected in a Japanese patient with unknown hepatitis in 1997. Subsequently, several studies performed to evaluate different aspects of Torque teno virus pathogenesis.

Objectives

The present study aimed to determine dominant genotype of Torque teno virus in chronic hepatitis disease using 5΄-UTR sequence among patients infected by hepatitis C virus in Shiraz – Iran.

Patients and Methods

The study conducted in 240 patients with chronic hepatitis C from Prof. Alborzi Clinical Microbiology Research Center. The presence of Torque teno virus DNA and its genotype in plasma was assessed by nested polymerase chain reaction using two primer sets for 5΄-UTR and N22 regions. Phylogenetic analysis was performed based on 5΄-UTR region.

Results

DNA of Torque teno virus was detected in 220 out of 240 (92 %) patients with chronic hepatitis C by the use of 5΄-UTR primer based PCR method and in 12 out of 240 (5%) by the use of N22 primer. Based on phylogenetic analysis it was shown that the Dominant genotype in this study was 11. Genotypes 1, 3, 17, and 22 were also detected. Some sequences could not be classified to a specific genotype.

Conclusions

The prevalence of Torque teno virus DNA in patients with chronic hepatitis C disease by the use of 5΄-UTR primer appeared to be higher compared to that revealed by N22 primer. We observed five genotypes among hepatitis C chronic patients in our study.     

Hepatitis B Virus Vaccine for Patients with Hepatitis C Virus Infection

Summary Hepatitis C is a disease with varying rates of progression. The role of hepatitis B virus (HBV) as a cofactor in the development of hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC) has been suggested and the use of HBV vaccine in all HCV-infected patients has been advocated. This review presents the implications of HBV and HCV coinfection and addresses the issues of HBV vaccine immunogenicity and safety in patients with chronic HCV infection. Received: December, 1999 · Revision accepted: July 1, 2000     

The Association of Human Immunodeficiency Virus Infection with Spontaneously Resolved Hepatitis C Virus Infection and Level of Viremia Among Injection Drug Users

This study aimed to investigate whether HIV and HIV-related factors are associated with spontaneously resolved hepatitis C virus (HCV) infection and levels of hepatitis C viremia. Among 351 anti-HCV(+) injection drug users, with and without HIV infection, multivariate methods were used to evaluate whether HIV status and HIV viral load, CD4 T-cell count, and concurrent HIV antiretroviral therapy were associated with (1) spontaneously resolved HCV infection and (2) HCV RNA levels. In 186 HIV patients, decreased HCV resolution was independently associated with Black race and modestly associated with CD4 T-cell count <200 cells/ml. Among 310 patients with persistent HCV infection, higher HCV RNA levels were independently associated with HIV status but not with other HIV-related factors. HIV may be associated with persistent HCV infection in patients with low CD4 T-cell counts. Moreover, HIV is associated with increased HCV viral load, which may attenuate response to HCV antiviral treatment in coinfected patients.     

Clinical Significance of Hepatitis GB Virus C Infection in Alcoholic Liver Disease

Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and γ-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.     

初步探讨丙型肝炎病毒体外感染的致病机理

目的:初步探讨原代培养肝细胞对HCV的易感性,并在此基础上观察HCV感染后肝细胞形态学的变化。方法:用HCV RNA阳性血清与培养肝细胞共同孵育后,收集不同时相点标本,以逆转录聚合酶链反应(RT-PCR)、分别细胞内或上清中正负链RNA,免疫组化检测细胞内HCV NS3、NS5抗原的表达以及原位杂交检测细胞内HCV负链RNA,同时在电镜下观察细胞形态学变化。结果:接种感染血清后第3～5d,即可在细胞内或培养上清中检出HCV正负链RNA;感染肝细胞内可见HCV NS3、NS5抗原表达,阳性物质位于胞浆中;原位杂交法证实细胞内存在负链RNA,也位于胞浆中;光镜下未发现感染细胞形态学变化,电镜下发现胞浆内含有大量的脂肪空泡、多泡体,并可见疑似病毒样结构。结论:HCV不但能感染树鼩肝细胞,而且在体外能直接致细胞病变。     

Prevalence and Clinical Significance of Hepatitis C Virus Infection in Thai Patients with Thalassemia

Hepatitis C virus (HCV) infection is a common cause of liver disease in thalassemia major patients in Western, especially Mediterranean, countries. Its significance in thalassemic patients from Southeast Asia has not been critically evaluated. In this report, we describe our study of the prevalence of HCV infection among Thai patients with thalassemia. The relationships of the infection to blood transfusion and the infection's effects on liver function have also been determined. Of the 104 patients studied, 21 (20.2%) tested positively by enzyme immunoassay for anti-HCV antibody, whereas only 2 patients (2%) had the hepatitis B surface antigen. There was no significant relationship between the presence of anti-HCV antibodies and the number and frequency of blood transfusions. In fact, 2 patients (10%) who tested positive for anti-HCV antibodies had never received transfusions. Patients with anti-HCV antibodies had significantly abnormal liver functions, such as higher levels of serum aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) and lower levels of serum albumin, compared with patients without anti-HCV antibodies (P = .021, .017, and .004, respectively). However, there were also significant correlations between iron status as indicated by transferrin saturation or serum ferritin levels and SGOT, SGPT, and gamma-glutamyltransferase (GGT) levels. Moreover, abnormal liver function as represented by elevated levels of SGOT, SGPT, GGT, and serum alkaline phosphatase was observed more frequently in patients with iron overload than in patients with a lower degree of iron burden. The presence of HCV did not alter the effects of iron overload on liver function. The findings suggest that both HCV and iron overload are the main causes of abnormal liver function in Thai patients with thalassemia. The treatment of both problems, if coexisting in patients with thalassemia, is required to prevent progression to chronic liver disease.     

丙型肝炎病毒对SMMC 7721细胞体外直接致病作用的研究

目的:探讨丙型肝炎病毒(HCV)的直接致病作用。方法:用HCV阳性血清体外感染SMMC 7721细胞,观察细胞形态的变化,并运用四甲基偶氮唑盐(MTT)法及流式细胞仪(FCM)分别检测培养细胞的存活率及凋亡率,同时用套式逆转录-聚合酶链反应(nest RT-PCR)检测其中的正、负链HCV RNA。结果:HCV感染后部分SMMC7721细胞发生皱缩、脱壁,8h细胞存活率为74.2％,细胞凋亡率为18.7％,至56h后细胞存活率回复至84.3％以上,而细胞凋亡率又降至7.4％以下;各时间组的细胞存活率显著低于未感染HCV的SMMC7721细胞,而凋亡率则显著高于未感染的SMMC 7721细胞。感染后24h细胞及上清中HCV RAN检测结果均阴性,48h后在细胞中可检出正、负链HCV RNA,96h后细胞中HCV RNA正链呈阳性、负链转为阴性。结论:1.HCV具有一定的直接致病作用;2.HCV感染SMMC7721后的复制不稳定。